tbuckley/cabot-search huggingface dataset:
Abstract P1-10-03: Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series
Authors: Leticia Hernandes de Brito, Felipe Cicci Farinha Restini, Maria Thereza Mansur Starling, Gabriela Silva Moreira de Siqueira, Gustavo Nader Marta, Heloisa de Andrade Carvalho, Samir Abdallah Hanna
Journal: Cancer Research (2023)

Abstract INTRODUCTION Extreme hypofractionation in patients with early-stage breast cancer has been studied in randomized phase III non-inferiority trials. There is scarce data on this strategy in Latin American patients. OBJECTIVES To describe the profile of patients diagnosed with breast cancer treated with radiotherapy with an ultra-hypofractionated regimen (5 fractions of 5.2 Gy, in one week), as well as the dosimetric aspects and acute toxicity related to the treatment. METHOD Retrospective cohort through a Brazilian uni-institutional series, with analysis of pathological, dosimetric, and toxicity variables. RESULTS Between May 2020 and March 2022, 67 patients were included, with a median age at diagnosis of 71 years (41-93). Regarding staging, 25.8% had in situ tumors, 60.6% of patients were IA, and only 3% were stage IIA. Nineteen percent of patients had histological grade 3; 24.6%, had nuclear grade 3. Hormone receptors were positive in 92.1% of patients. The mean ki67 was 19%, and HER2 was negative at 84.5%. All patients underwent conservative surgery, and 5 underwent reconstruction with autologous flaps. Fifty-one patients underwent hormone therapy and only 2 underwent adjuvant chemotherapy. All but two patients were treated with the conformal technique (VMAT was used due to unfavorable anatomy). The mean volume of the irradiated breast was 926 cm3 (ranging from 920 to 932 cm3). Regarding the constraints of the organs at risk, the average V8Gy of the ipsilateral lung was 11.4%, ranging from 0 to 24%. In the heart, the average volumes receiving 1.5Gy and 7Gy were, respectively, 9.2% and 0.7%. No patient had acute toxicity greater than grade 2. The effects on the skin appeared on average 20 days after the end of treatment, with resolution in a maximum of 3 months. The median follow-up time was 10 months (3 - 26). We did not observe any case of local-recurrence, of breast-cancer-related death. CONCLUSION Although our follow-up time is premature, we have found that ultra-hypofractionated radiotherapy was feasible, tolerable, and safe, for patients with early breast cancer. Also, the constraints on the organs at risk were respected. There were no high-grade acute toxicities. Besides convenience, ultra-hypofractionation can improve access to radiotherapy in resource-scarce settings. Citation Format: Leticia Hernandes de Brito, Felipe Cicci Farinha Restini, Maria Thereza Mansur Starling, Gabriela Silva Moreira de Siqueira, Gustavo Nader Marta, Heloisa de Andrade Carvalho, Samir Abdallah Hanna. Ultra-hypofractionated Radiotherapy for Breast Cancer: A Brazilian Single-Institutional Series [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-03.
Abstract P1-13-01: Targeting RRM2 for the treatment of palbociclib resistant breast cancer
Authors: Nahid Sultana, Howard L. Elford, Jesika S. Faridi
Journal: Cancer Research (2023)

Abstract Hormone receptor (HR) positive breast cancer (BC) is a prevalent disease accounting for almost 2 million new cases globally. Almost 70-80% of breast cancer patients are women with a positive score for the estrogen receptor (ER). HR positive BCs of all stages are selectively treated with endocrine therapy targeting ER activity. Intrinsic and acquired resistance are common phenomena, impacting patient outcomes negatively. Palbociclib is an FDA approved checkpoint inhibitor for the treatment of HR+/HER2- breast cancer in combination with aromatase inhibitors or selective estrogen receptor degraders. However, patients responding well to the therapy in the beginning, lose sensitivity to palbociclib with time. Ribonucleotide reductase (RR) is a rate limiting enzyme in DNA synthesis consisting of two subunits RRM1 and RRM2. In our previous study, we have shown that RRM2 is upregulated in ER positive tamoxifen resistant BC. Previously, we have also reported that didox (DDX) which is a unique RRM2 enzyme inhibitor can significantly halt malignant breast cancer cell division in combination with an anthracycline drug doxorubicin by targeting RRM2, mutant p53 and NFkB regulatory proteins. In this study, we target palbociclib resistant BC with DDX to circumvent palbociclib resistance. For this purpose, we have developed palbociclib resistant ER positive MCF7 and ER negative MDA-MB-468 breast cancer cell lines. Here, we report morphological changes in parental as compared to palbociclib resistant cells after treatment with palbociclib alone, DDX alone or with palbociclib as compared to non-treated cells. Cell proliferation studies confirm the synergistic combinatorial effect of palbociclib and DDX compared to palbociclib or DDX alone. We also report that DDX alone or in combination with palbociclib downregulates cell cycle and NFkB proteins in palbociclib resistant ER positive MCF7 and ER negative MBA-MB-468 breast cancer cell lines. Citation Format: Nahid Sultana, Howard L. Elford, Jesika S. Faridi. Targeting RRM2 for the treatment of palbociclib resistant breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-13-01.
Abstract OT2-08-01: A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC)
Authors: Tao Sun, Liang Zhang
Journal: Cancer Research (2023)

Abstract Background: PD-1/PD-L1 inhibitor plus chemotherapy have shown tolerability and significant clinical benefits in pts with advanced TNBC. As antiangiogenic agent could remodel tumor blood vessels and increase the response to immune-checkpoint inhibitors (ICIs), we designed an investigator initiated trial (IIT) to investigate the efficacy and safety of AK105 (anti-PD-1 antibody), anlotinib (antiangiogenic, multi-target tyrosine kinase inhibitor) combined with nab-P as a first-line therapy in pts with advanced TNBC. Method: In this multicenter, prospective, single arm, phase 2 study, eligible pts were female aged 18-75 years, with ECOG PS 0-1, who had locally advanced or recurrent/metastatic triple-negative (estrogen receptor-, progesterone receptor- and HER2-) breast cancer. The main exclusive criteria were previous use of PD-1/PD-L1 antibody, cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) antibody or antiangiogenic agent, and central nervous system (CNS) metastases. Eligible pts were treated with intravenous AK105(200mg on day 1), oral anlotinib(12mg once daily on days 1-14) and intravenous nab-P (125mg/m2 on days 1 and 8). The triplet combination regimen repeated every 21 days until disease progression, death or intolerable toxicity. The primary endpoint is overall response rate (ORR), and the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety. Simon’s two-stage design were used to calculate the sample size assuming ORR is improved from 45.9% (nab-P alone) to 65% (AK105, anlotinib combined with nab-P) with the power (1-β) taken as 0.80 and the type I error (α) taken as 0.05 (two-sided). Enrollment began in June 2022 with a total goal of 42 pts at 7 sites in China. Clinical trial information: NCT05244993. Research Sponsor: Chia Tai Tianqing Pharmaceutical Group Co., Ltd. Citation Format: Tao Sun, Liang Zhang. A prospective phase 2 study on efficacy and safety of AK105, anlotinib combined with nab-paclitaxel (nab-P) as a first-line therapy in patients(pts) with advanced triple-negative breast cancer(TNBC). [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-08-01.
Abstract P1-10-07: Role of postmastectomy radiation therapy in breast cancer patients according to pathologic nodal status after neoadjuvant chemotherapy
Authors: Dowook Kim, Jin Ho Kim, In Ah Kim, Ji Hyun Chang, Kyung Hwan Shin
Journal: Cancer Research (2023)

Abstract Purpose: The role of post-mastectomy radiation therapy (PMRT) in breast cancer patients after neoadjuvant chemotherapy (NAC) is highly controversial. This study aimed to evaluate the impact of PMRT according to pathologic nodal status. Methods and Materials: We retrospectively reviewed 682 patients with clinical stage II-III breast cancer who underwent NAC and mastectomy from 2013 to 2017. Of total, 596 (87.4%) received PMRT and 86 (12.6%) did not. We investigated the relationship amongst locoregional recurrence-free survival (LRRFS), disease-free survival (DFS), overall survival (OS), and various prognostic factors. Subgroup analyses to identify the patients who may benefit from PMRT were also performed. Results: The median follow-up duration was 67 months. In ypN+ patients (n = 368, 51.2%), PMRT showed significant benefit for LRRFS, DFS, and OS (all p &amp;lt; 0.001). Based on multivariate analysis, histologic grade (HG) III (hazard ratio [HR] = 3.67, p = 0.002), lymphovascular invasion (LVI) (HR = 2.38, p = 0.045), and ypN2-3 (HR = 2.37, p = 0.02) were identified as significant risk factors for poor LRRFS. In ypN1 patients with more than two factors among (i) luminal subtype (ii) HG I-II and (iii) absence of LVI, PMRT showed no significant difference in LRRFS (p = 0.18). In ypN0 patients (n = 351, 48.8%), PMRT was not significantly associated with LRRFS, DFS, and OS. However, PMRT showed better LRRFS in triple-negative breast cancer (TNBC) subtype (p = 0.04). Conclusion: PMRT had a high impact on treatment outcomes in patients with residual lymph nodes following NAC and mastectomy. Among the ypN0 patients, PMRT may be beneficial only in the TNBC subtype. Citation Format: Dowook Kim, Jin Ho Kim, In Ah Kim, Ji Hyun Chang, Kyung Hwan Shin. Role of postmastectomy radiation therapy in breast cancer patients according to pathologic nodal status after neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-10-07.
Abstract P2-11-21: Outcomes and Treatment Pattern in Women With 1 cm or Smaller, Node-Negative Hormone Receptor-negative Breast Cancer in Fudan University Shanghai Cancer Center
Authors: Xiyu Liu, Min He
Journal: Cancer Research (2023)

Abstract Background: To evaluate the outcome the treatment pattern in women diagnosed with T1mic, T1a and T1b, node-negative, hormone receptor (HR) –negative breast cancer. Methods: This was a retrospective cohort study within the Fudan University Shanghai Cancer Center (FUSCC) that included 605 women with T1mic,a,bN0M0 breast cancer treated between 2010 and 2020. Tumors were grouped by size (T1mic, T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. Kaplan-Meier product was used to calculate invasive disease-free survival (iDFS), breast cancer-specific survival (BCSS) and overall survival (OS). Results: Median follow-up time was 5.0 years. Seventy-three percent of patients with triple-negative breast cancer (TNBC) were treated with chemotherapy. For those with HER2- positive breast cancers, 82% received chemotherapy, and 71% received trastuzumab. The treatment pattern varied over the years, with a downward trend of chemotherapy in TNBC and an upward trend of trastuzumab in HER2-positive breast cancer. Survival outcomes diverged by subtype and size. In this retrospective cohort study, the 5-year DFS for treated patients with T1mic,a tumors ranged from 96.2% to 97.7%, and for patients with T1b tumors, it ranged from 92.1% to 95.0%. The 5-year DFS for patients with T1mic,a tumors untreated with chemotherapy or trastuzumab was 100%. The 5-year DFS for TNBC patients with T1b tumors untreated with chemotherapy was 90.5%, while for HER2-positive patients with T1b tumors untreated with chemotherapy or trastuzumab it was 87.5%, Conclusion: Women with T1mic,a tumors have an excellent prognosis without chemotherapy or trastuzumab, representing an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks. Figure 1 Systematic Treatment Pattern of Patients With T1mic, a, b N0 Patients With Triple-negative or HER2-positive Breast Cancer from 2010 to 2020 Figure 1 Systematic Treatment Pattern of Patients With T1mic, a, b N0 Patients With Triple-negative or HER2-positive Breast Cancer from 2010 to 2020 Table 1. Patient Demographics and Clinicopathologic Characteristics for T1mic, a, b N0 Patients With Triple-negative or HER2-positive Breast Cancer, FUSCC 2010-2020 Table 2 Systematic Treatment of Patients With T1mic, a, b N0 Patients With Triple-negative or HER2-positive Breast Cancer, FUSCC 2010-2020 Citation Format: Xiyu Liu, Min He. Outcomes and Treatment Pattern in Women With 1 cm or Smaller, Node-Negative Hormone Receptor-negative Breast Cancer in Fudan University Shanghai Cancer Center [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-21.
Abstract P2-11-09: Association of 21-gene recurrence score with overall survival in phase 3 TAILORx trial
Authors: Sherry X. Yang, John Yu, Molin Wang
Journal: Cancer Research (2023)

Abstract Background: The 21-gene recurrence score (RS) assay is a prognostic measurement originally established for distant recurrence in estrogen receptor-positive and node-negative breast cancer. Retrospective studies and the Trial Assigning Individualized Options for Treatment (TAILORx; ClinicalTrials.gov NCT00310180) validated its significance besides testing chemotherapy benefit in patients with midrange RS (11-25). However, unclarity remains as to whether RS has comparable prognostic value for overall survival (OS) in the TAILORx trial population. Methods: Association between the recurrence scores (midrange or high-range 26-100 vs. low-range 0-10) and OS was evaluated in all eligible patients with clinicopathological and treatment information by multivariable Cox proportional hazards regression model including RS, tumor size, tumor grades, chemotherapy, endocrine regimens, surgery type, progesterone receptor and demographics. We also evaluated the association between RS and invasive disease-free survival (DFS), recurrence-free interval (RFI) or distant recurrence-free interval (dRFI) by multivariable Cox analysis. Results: Median follow-up was 95.5 (range 0.1 to 138.6) months for OS, 89.6 months (range 0 to 134.8) for DFS, 87.7 (range 0 to 134.8) months for RFI or 87.6 (range 0-134.8) months for dRFI. Compared with low score group, midrange and high-range scores were associated with RFI and dRFI, respectively (P≤0.01 each). However, midrange score was neither associated with OS (adjusted HR 1.15; 95% CI 0.87-1.52; P=0.33) nor associated with DFS (HR 1.16; 95% CI 0.97-1.38; P=0.11). High-range score was associated with DFS (HR 1.58; 95% CI 1.21-2.06; P&amp;lt; 0.01) and had a trend towards association with OS (HR 1.44; 95% CI 0.95-2.19; P=0.08). Conclusions: The data indicate that the recurrence scores provide independent prognosis for breast cancer recurrence at both distant and locoregional sites and for distant recurrence, respectively. High-range score is prognostic of disease-free survival, with the midrange score showing marginal association. Midrange and high-range recurrence scores do not provide independent prognostic information for overall survival in hormone receptor-positive, HER2-negative, node-negative breast cancer in the TAILORx trial population. Citation Format: Sherry X. Yang, John Yu, Molin Wang. Association of 21-gene recurrence score with overall survival in phase 3 TAILORx trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-11-09.
Abstract MS1-3: Treatment of ER+/HER2+ breast cancer
Authors: Stephen Johnston
Journal: Cancer Research (2023)

Abstract Co-expression of hormone receptors (HR) and human epidermal growth factor receptor 2 (HER2) occurs in 10% of all breast cancers, and due to cross-talk mechanisms that influence cell signalling the co-expression of these receptors modulates response of these cancers to both HER2-directed and endocrine therapies. Prior to the advent of HER2 targeted therapies, patients with HR+/HER2+ breast cancer had a significantly worse prognosis compared with HR+/HER2- breast tumours, primarily related to HER2 signalling driving endocrine resistance. Likewise, prior clinical studies in the neoadjuvant setting showed that patients with HR+/HER2+ primary breast cancer had a lower pathological complete response rate to HER2-targeted therapy plus chemotherapy that those with HR-/HER2+ tumours, suggesting a different biology. As such, strategies that combine receptor blockade against HER2 and HR have been developed in metastatic breast cancer (MBC), confirming that combined blockade is better than endocrine therapy (ET) alone, and then that dual HER2 blockade + ET was superior to single HER2 therapy + ET. More recently combinations of a CDK 4/6 inhibitor with ET and HER2 therapy has shown significant clinical efficacy and survival benefit in heavily pre-treated patients, confirming the efficacy for non-chemotherapy targeted combinations in HR+/HER2+ MBC. In the early breast cancer (EBC) setting, most HER2 directed therapy is given in combination with chemotherapy in the neoadjuvant setting, while studies of combined ET and HER2 targeted strategies without chemotherapy work slower with lower pCR rates. As such, the real benefit for combined targeted therapy may be in the adjuvant setting where ET and HER2 therapy are routinely given together following completion of chemotherapy. Furthermore, extended adjuvant ET/HER2 therapy beyond completion of antibody based treatment may also provide extra benefit, and in higher risk patients longer treatment may prove an important consideration. Citation Format: Stephen Johnston. Treatment of ER+/HER2+ breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr MS1-3.
Abstract P1-11-16: Treatment with tyrosine kinase inhibitors (TKIs) in HER2-positive metastatic breast cancer after trastuzumab emtansine (T-DM1) failure: A real-world study
Authors: Yongmei Yin, Wei Li, Xiang huang, Chunxiao Sun, Yijia Hua, Nan Jin, Xinyu Wu
Journal: Cancer Research (2023)

Abstract Background Trastuzumab emtansine (T-DM1) has shown great effectiveness in treating HER2-positive metastatic breast cancer, but therapies subsequent to T-DM1 failure remain controversial. Here, we investigated efficacy and safety of tyrosine kinase inhibitors (TKIs) based therapy in T-DM1 resistant HER2-positive metastatic breast cancer. Methods From August 2019 to April 2022, 53 HER2-positive metastatic breast cancer patients received TKIs-based therapy after T-DM1 failure in Jiangsu Province Hospital. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and safety profiles were reported. Results 53 patients received TKIs-based therapies as a second or later line therapy. 51 (96.2%) patients received a combined therapy, including TKIs plus capecitabine, vinorelbine or trastuzumab. 2 (3.7%) patients received TKIs alone. The median follow-up time was 19.7 months (95%CI 15.4-24.0). The median PFS was 11.9 months (95%CI 7.9-15.9). OS has not reached. ORR was 19.6% and CBR was 72.5%. For patients who had brain metastasis (n=12), the median PFS was 10.5 months (95%CI 7.5-13.5) and intracranial ORR was 33.3%. Compared with lapatinib (n=30), pyrotinib (n=21) provided a better PFS after T-DM1 progression (8.0 months vs. 19.0 months, P=0.033). The most common adverse events were thrombocytopenia (12, 23.6%), diarrhea (8, 15.7%), leucopenia (8, 15.7%) and hand-foot syndrome (8, 15.7%). Conclusion TKIs-based therapy could prolong the survival of HER2-positive metastatic breast cancer patients after T-DM1 failure, including those with brain metastases. Compared with lapatinib, pyrotinib might provide better outcomes for overcoming T-DM1 resistance. Citation Format: Yongmei Yin, Wei Li, Xiang huang, Chunxiao Sun, Yijia Hua, Nan Jin, Xinyu Wu. Treatment with tyrosine kinase inhibitors (TKIs) in HER2-positive metastatic breast cancer after trastuzumab emtansine (T-DM1) failure: A real-world study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-11-16.
Abstract ED7-2: Multiplex spatial proteomic profiling
Authors: David Rimm
Journal: Cancer Research (2023)

Abstract Multiplex spatial analysis is touted as a potential solution for tissue biomarkers for prognostic and companion diagnostic applications. Spatial analysis infers maintaining the location of a biomolecule so that both its amount and context can contribute to the information obtained. Immunohistochemistry (IHC) is the archetypal method of spatial profiling and the only application that has made it to the clinic. In this session, we will discuss technologies based on IHC, but that allow assessment of at least two, and as many as 100 or more proteins within the cell or molecular compartment that maintains spatial context. The simplest and most common approach is multiplex immunofluorescence, followed by a number of next generation techniques that use alternative labeling of the antibodies or cycling strategies or both to generate spatially informed data. Excluding Mass spectrometry-based methods, still in early stages, the highest “plex” method for protein is digital spatial profiling. Digital spatial profiling (DSP) uses a molecular method to define spatial compartments which is different from other high-plex methods that use cell segmentation, an image analysis method that largely depends on the presence of a cell nucleus in the image. As a result, the DSP method allows assessment of both cellular and non-cellular stromal compartments. DSP and other high-plex methods that will be discussed are thought to be best used as biomarker discovery tools, that might find biomarkers that can be measured with a more traditional approach for assessment in the clinic. Citation Format: David Rimm. Multiplex spatial proteomic profiling [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr ED7-2.